Abstract：
:The high Aβ42/Aβ40 production ratio is a hallmark of familial Alzheimer's disease, which can be caused by mutations in the amyloid precursor protein (APP). The C-terminus of Aβ is generated by γ-secretase cleavage within the transmembrane domain of APP (APPTM), a process that is primed by an initial ε-cleavage at either T48 or L49, resulting in subsequent production of Aβ42 or Aβ40, respectively. Here we solve the dimer structures of wild-type APPTM (AAPTM WT) and mutant APPTM (FAD mutants V44M) with solution NMR. The right-handed APPTM helical dimer is mediated by GXXXA motif. From the NMR structural and dynamic data, we show that the V44M and V44A mutations can selectively expose the T48 site by weakening helical hydrogen bonds and increasing hydrogen-deuterium exchange rate (kex). We propose a structural model in which FAD mutations (V44M and V44A) can open the T48 site γ-secretase for the initial ε-cleavage, and consequently shift cleavage preference towards Aβ42.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Chen W,Gamache E,Rosenman DJ,Xie J,Lopez MM,Li YM,Wang Cdoi
10.1038/ncomms4037subject
Has Abstractpub_date
2014-01-01 00:00:00pages
3037issn
2041-1723pii
ncomms4037journal_volume
5pub_type
杂志文章abstract：:Urinary sodium and potassium excretion are associated with blood pressure (BP) and cardiovascular disease (CVD). The exact biological link between these traits is yet to be elucidated. Here, we identify 50 loci for sodium and 13 for potassium excretion in a large-scale genome-wide association study (GWAS) on urinary s...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-019-11451-y
更新日期：2019-08-13 00:00:00
abstract：:Controlling the transmission of electrical current using a quantum point contact constriction paved a way to a large variety of experiments in mesoscopic physics. The increasing interest in heat transfer in such systems fosters questions about possible manipulations of quantum heat modes that do not carry net charge (...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-017-02433-z
更新日期：2017-12-21 00:00:00
abstract：:Glucose-induced insulin secretion is an essential function of pancreatic β-cells that is partially lost in individuals affected by Type 2 diabetes. This unique property of β-cells is acquired through a poorly understood postnatal maturation process involving major modifications in gene expression programs. Here we sho...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms9084
更新日期：2015-09-02 00:00:00
abstract：:Light-phase-sensitive techniques, such as coherent multidimensional spectroscopy, are well-established in a broad spectral range, already spanning from radio-frequencies in nuclear magnetic resonance spectroscopy to visible and ultraviolet wavelengths in nonlinear optics with table-top lasers. In these cases, the abil...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms15626
更新日期：2017-05-30 00:00:00
abstract：:Functional blood vessel growth depends on generation of distinct but coordinated responses from endothelial cells. Bone morphogenetic proteins (BMP), part of the TGFβ superfamily, bind receptors to induce phosphorylation and nuclear translocation of SMAD transcription factors (R-SMAD1/5/8) and regulate vessel growth. ...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms13247
更新日期：2016-11-11 00:00:00
abstract：:Chemical utilization of vast fossil and renewable feedstocks of methane remains one of the most important challenges of modern chemistry. Herein, we report direct and selective methane photocatalytic oxidation at ambient conditions into carbon monoxide, which is an important chemical intermediate and a platform molecu...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-019-08525-2
更新日期：2019-02-11 00:00:00
abstract：:Myoblast fusion is an indispensable step for skeletal muscle development, postnatal growth, and regeneration. Myeloid differentiation primary response gene 88 (MyD88) is an adaptor protein that mediates Toll-like receptors and interleukin-1 receptor signaling. Here we report a cell-autonomous role of MyD88 in the regu...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-017-01866-w
更新日期：2017-11-20 00:00:00
abstract：:Enzymatic digestion for protein sequencing usually requires much time, and does not always result in high sequence coverage. Here we report the use of aqueous microdroplets to accelerate enzymatic reactions and, in particular, to improve protein sequencing. When a room temperature aqueous solution containing 10 µM myo...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-020-14877-x
更新日期：2020-02-26 00:00:00
abstract：:Primitive carbonaceous chondrites contain a large array of organic compounds dominated by insoluble organic matter (IOM). A striking feature of this IOM is the systematic enrichment in deuterium compared with the solar hydrogen reservoir. This enrichment has been taken as a sign of low-temperature ion-molecule or gas-...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms9567
更新日期：2015-10-13 00:00:00
abstract：:Ni/Fe oxyhydroxides are the best performing Earth-abundant electrocatalysts for water oxidation. However, the origin of their remarkable performance is not well understood. Herein, we employ spectroelectrochemical techniques to analyse the kinetics of water oxidation on a series of Ni/Fe oxyhydroxide films: FeOOH, FeO...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-019-13061-0
更新日期：2019-11-15 00:00:00
abstract：:Dense ceramic materials can form in nature under mild temperatures in water. By contrast, man-made ceramics often require sintering temperatures in excess of 1,400 °C for densification. Chemical strategies inspired by biomineralization processes have been demonstrated but remain limited to the fabrication of thin film...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms14655
更新日期：2017-03-06 00:00:00
abstract：:A number of marine organisms use muscle-controlled surface structures to achieve rapid changes in colour and transparency with outstanding reversibility. Inspired by these display tactics, we develop analogous deformation-controlled surface-engineering approaches via strain-dependent cracks and folds to realize the fo...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms11802
更新日期：2016-07-08 00:00:00
abstract：:The modern energy economy and environmental infrastructure rely on the flow of fluids through fractures in rock. Yet this flow cannot be imaged directly because rocks are opaque to most probes. Here we apply chattering dust, or chemically reactive grains of sucrose containing pockets of pressurized carbon dioxide, to ...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-020-19087-z
更新日期：2020-10-19 00:00:00
abstract：:Large-scale genomic analyses of human cancers have cataloged somatic point mutations thought to initiate tumor development and sustain cancer growth. However, determining the functional significance of specific alterations remains a major bottleneck in our understanding of the genetic determinants of cancer. Here, we ...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-017-01519-y
更新日期：2017-12-12 00:00:00
abstract：:The accurate measurement of microscopic force fields is crucial in many branches of science and technology, from biophotonics and mechanobiology to microscopy and optomechanics. These forces are often probed by analysing their influence on the motion of Brownian particles. Here we introduce a powerful algorithm for mi...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-018-07437-x
更新日期：2018-12-04 00:00:00
abstract：:Non-covalent π-π interactions are central to chemical and biological processes, yet the full understanding of their origin that would unite the simplicity of empirical approaches with the accuracy of quantum calculations is still missing. Here we employ a quantum-mechanical Hamiltonian model for van der Waals interact...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms14052
更新日期：2017-02-07 00:00:00
abstract：:The spindle assembly checkpoint (SAC) arrests cells in mitosis by sensing unattached kinetochores, until all chromosomes are bi-oriented by spindle microtubules. Kinetochore accumulation of the SAC component Mad1-Mad2 is crucial for SAC activation. However, the mechanism by which Mad1-Mad2 accumulation at kinetochores...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms10151
更新日期：2016-01-08 00:00:00
abstract：:The alloy-design strategy of combining multiple elements in near-equimolar ratios has shown great potential for producing exceptional engineering materials, often known as 'high-entropy alloys'. Understanding the elemental distribution, and, thus, the evolution of the configurational entropy during solidification, is ...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms6964
更新日期：2015-01-20 00:00:00
abstract：:The long external filament of bacterial flagella is composed of several thousand copies of a single protein, flagellin. Here, we explore the role played by lysine methylation of flagellin in Salmonella, which requires the methylase FliB. We show that both flagellins of Salmonella enterica serovar Typhimurium, FliC and...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-020-15738-3
更新日期：2020-04-24 00:00:00
abstract：:In retinitis pigmentosa, loss of cone photoreceptors leads to blindness, and preservation of cone function is a major therapeutic goal. However, cone loss is thought to occur as a secondary event resulting from degeneration of rod photoreceptors. Here we report a genome editing approach in which adeno-associated virus...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms14716
更新日期：2017-03-14 00:00:00
abstract：:The physical nature of the bacterial chromosome has important implications for its function. Using high-resolution dynamic tracking, we observe the existence of rare but ubiquitous 'rapid movements' of chromosomal loci exhibiting near-ballistic dynamics. This suggests that these movements are either driven by an activ...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms4854
更新日期：2014-05-30 00:00:00
abstract：:Currently, there is no comprehensive framework to evaluate the evolutionary forces acting on genomic regions associated with human complex traits and contextualize the relationship between evolution and molecular function. Here, we develop an approach to test for signatures of diverse evolutionary forces on trait-asso...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-020-17258-6
更新日期：2020-07-24 00:00:00
abstract：:Quantized dynamics is essential for natural processes and technological applications alike. The work of Thouless on quantized particle transport in slowly varying potentials (Thouless pumping) has played a key role in understanding that such quantization may be caused not only by discrete eigenvalues of a quantum syst...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-020-17510-z
更新日期：2020-07-27 00:00:00
abstract：:Ataxia telangiectasia is caused by mutations in ATM and represents a paradigm for cancer predisposition and neurodegenerative syndromes linked to deficiencies in the DNA-damage response. The role of ATM as a key regulator of signalling following DNA double-strand breaks (DSBs) has been dissected in extraordinary detai...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms4347
更新日期：2014-02-27 00:00:00
abstract：:Nanophotonics is becoming invaluable for an expanding range of applications, from controlling the spontaneous emission rate and the directionality of quantum emitters, to reducing material requirements of solar cells by an order of magnitude. These effects are highly dependent on the near field of the nanostructure, w...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms13950
更新日期：2016-12-20 00:00:00
abstract：:Although hexagonal boron nitride (h-BN) is a good candidate for gate-insulating materials by minimizing interaction from substrate, further applications to electronic devices with available two-dimensional semiconductors continue to be limited by flake size. While monolayer h-BN has been synthesized on Pt and Cu foil ...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms9662
更新日期：2015-10-28 00:00:00
abstract：:Melting of the Greenland Ice Sheet is a leading cause of land-ice mass loss and cryosphere-attributed sea level rise. Blooms of pigmented glacier ice algae lower ice albedo and accelerate surface melting in the ice sheet's southwest sector. Although glacier ice algae cause up to 13% of the surface melting in this regi...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-020-20627-w
更新日期：2021-01-25 00:00:00
abstract：:Molecularly defined subclassification is associated with phenotypic malignancy of glioblastoma (GBM). However, current understanding of the molecular basis of subclass conversion that is often involved in GBM recurrence remain rudimentary at best. Here we report that canonical Wnt signalling that is active in proneura...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms12885
更新日期：2016-10-04 00:00:00
abstract：:Precise manipulation and control of coherent lattice oscillations via nanostructuring and phonon-wave interference has the potential to significantly impact a broad array of technologies and research areas. Resolving the dynamics of individual phonons in defect-laden materials presents an enormous challenge, however, ...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms11230
更新日期：2016-04-15 00:00:00
abstract：:The interpretation of molecular vibrational spectroscopic signals in terms of atomic motion is essential to understand molecular mechanisms and for chemical characterization. The signals are usually assigned after harmonic normal mode analysis, even if molecular vibrations are known to be anharmonic. Here we obtain th...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-020-18211-3
更新日期：2020-08-28 00:00:00
